IMMUNOREGULATORY ROLE OF INTERLEUKIN-10 IN PATIENTS WITH INFLAMMATORY BOWEL-DISEASE

被引：380

作者：

SCHREIBER, S

HEINIG, T

THIELE, HG

RAEDLER, A

机构：

[1] UNIV HAMBURG, GASTROENTEROL SECT, HAMBURG, GERMANY

[2] UNIV HAMBURG, DEPT MED, DEPT IMMUNOL, HAMBURG, GERMANY

来源：

GASTROENTEROLOGY | 1995年 / 108卷 / 05期

关键词：

D O I：

10.1016/0016-5085(95)90692-4

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background/Aims: Active inflammatory bowel disease (IBD) is associated with increased proinflammatory cytokines. Deficiency of interleukin (IL) 10, a contrainflammatory cytokine, leads to the development of colitis in IL-10 knockout mice. We characterized IL-10 regulation of proinflammatory cytokine (tumor necrosis factor [TNF] alpha and IL-1 beta) expression in IBD in vitro and in vivo. Methods: IL-10 regulation of IL-1 beta, TNF-alpha, and IL-1 receptor antagonist expression by peripheral monocytes or isolated lamina propria mononuclear cells (LPMNC), respectively, was studied by enzyme-linked immunosorbent assay (cytokine secretion) and by semiquantitative reverse-transcription polymerase chain reaction. Results: IL-10 down-regulates IL-1 beta and TNF-alpha secretion as well as messenger RNA levels in IBD peripheral monocytes and LPMNC in a dose-dependent manner. In parallel, IL-1 receptor antagonist secretion is induced, and IL-10 can restore diminished in vitro IL-1 receptor antagonist/IL-1 beta ratios in IBD to normal levels. Equal concentrations of IL-10 are detectable in both normal and IBD intestinal lamina propria biopsy homogenates. After topical IL-10 enema treatment of three steroid therapy-refractory patients with ulcerative colitis, in vitro release of proinflammatory cytokines from IBD peripheral monocytes as well as LPMNC is dramatically down-regulated. Conclusions: IL-10 down-regulates the enhanced secretion as well as messenger RNA levels of proinflammatory cytokines by IBD mononuclear phagocytes in vitro. In vivo topical application of IL-10 induces down-regulation of proinflammatory cytokine secretion both systemically and locally.

引用

页码：1434 / 1444

页数：11

共 40 条

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